Risk of ischemic stroke associated with direct oral anticoagulants discontinuation on patients with non-valvular atrial fibrillation.

Introduction: Although direct oral anticoagulants' (DOACs) prescriptions have experienced immense growth in the last decade, the proportion of discontinuers is still common yielding an increased risk of ischemic stroke (IS) onset.

Aims: We aimed to estimate the association between DOACs discontinuation and risk of IS among patients with non-valvular atrial fibrillation (NVAF).

Methods: We used data from a cohort of new DOACs users, followed patients from the first DOAC prescription date up to IS (index date) and conducted a nested case-control analysis using conditional logistic regression. Adjusted odds ratios, 95% confidence intervals were calculated for discontinuation of DOACs (current use compared with past use). The latter, subdivided among those stopping treatment 3 to 2 months and 6 and 3 months prior to index date. The effect of naïve current users against IS onset compared with non-naïve current users was also evaluated.

Results: DOACs discontinuation showed an OR of IS of 1.47 (95% CI: 1.02-2.12); estimates were 2.51 (95% CI: 1.84-3.42) for whom discontinued treatment within months 3 and 2 and 1.43 (95% CI: 0.96-2.13) for those between months 6 and 3 prior to index date. Analyzing DOACs individually, risk of IS associated with past users compared with current users: 1.98 (95% CI: 1.25-3.12) for apixaban, 1.38 (95% CI: 0.40-4.72) for edoxaban, 1.98 (95% CI: 1.24-2.65) for dabigatran and 1.87 (95% CI: 1.26-2.76) for rivaroxaban. Similar results were found when stratified by naïve and non-naïve users.

Conclusions: DOACs' discontinuation is associated with higher risk of IS, especially in the second and third months following interruption.